2,3;5,6-Di-O-isopropylidene-1-O-(2-phenylacetyl)-α-d-mannofuranose

The title compound, C20H26O7, was prepared by esterification of 2,3;5,6-di-O-isopropylidene-α-d-mannofuranose with phenylacetic acid under standard DCC/DMAP (DCC = dicyclohexylcarbodiimide and DMAP = 4-dimethylaminopyridine) conditions. The solid-state structure confirms the retention of the α-configuration at the anomeric C atom. The compound is characterized by a relatively rigid framework with only a few degrees of freedom. Comparison with other di-O-isopropylidenemannofuranose derivatives shows the main differences to be associated with the flexible dimethyldioxolane ring, and that there are only small differences for the 2,3-O-isopropylidene-α-d-mannofuranose backbone. The packing is marked by a large number of weak C—H⋯O interactions.


Comment
The title compound, 1-O-(2-phenylacetyl)-2,3;5,6-di-O-isopropylidene-α-D-mannofuranose, was prepared as part of our ongoing work on the synthesis and metal-catalyzed decomposition of carbohydrate-derived diazo compounds (Sacui et al., 2008). It was prepared by esterification of commercially available 2,3;5,6-di-O-isopropylidene-α-D-mannofuranose with phenylacetic acid under standard DCC/DMAP (DCC = dicyclohexylcarbodiimide and DMAP = 4-dimethylaminopyridine) conditions. From 1 H NMR data, the precursor lactol (before esterification) exists in solution only as the α-anomer, which is in agreement with the reported solid state structure (Sheldrick et al., 1985;Miner et al., 2004). 1 H NMR data point in the same direction for the title compound. To obtain proof of the configuration of the title compound in the solid state we investigated its structure by single-crystal diffraction.
Slow evaporation of a solution of the compound in 95% ethyl alcohol led to formation of crystals of the title compound that could be analyzed by single-crystal diffraction. The compound crystallizes in an orthorhombic setting in P2 1 2 1 2 1 with one crystallographically independent molecule. The solid state structure confirms retention of the α-configuration at C-1 of the furanose ring under the conditions of the DCC-promoted esterification.
No strong directional intermolecular interactions are present in the structure of the title compound. For the carbohydrate part of the molecules the packing is instead marked by a large number of weaker C-H···O interactions as depicted in Fig. 2 (for numerical values, see Table 1). The phenyl rings are not involved in any π-π stacking interactions but instead they do group with the isopropylidene moieties to form layers perpendicular to the (110) plane characterized by the absence of any directional forces. Thus a semi-layered structure is created with alternating sections dominated by C-H···O interactions (the carbohydrate layers) and layers with only van der Waals / dispersion forces (the phenyl-isopropylidene layers).
All bond lengths and angles in the title compound are within the expected ranges for an organic compound. For the dihedral angles, most are fixed by the rigid backbone of the isopropylidene-mannofuranose skeleton, and the molecule exhibits only a few selected degrees of freedom. This becomes clearly apparent when, for example, comparing the title compound with other related compounds with a 2,3;5,6-di-O-isopropylidene-mannofuranose skeleton. A search in the Cambridge Crystallographic Database (version 5.31, 2010; Allen, 2002) revealed four related compounds, one of which has an L-mannofuranose sugar (BIRFUD, Aebischer et al., 1982), and one a β connection at carbon C1 (QEMKID, Zhao et al., 2006). The other two compounds are the lactol itself (CUFYIL, Sheldrick et al., 1985;Miner et al., 2004), and the 1-Omethyl derivative of the title compound (BOXQAG, Dang et al., 2001). Least square overlays of the latter two with the title compound are shown in Figs. 3a and 3b (title compound in red). The 2,3-O-isopropylidene-mannofuranose skeleton in all three compounds shows only small deviations and virtually all conformational differences are limited to the more flexible second isopropylidene moiety, which is rotated differently when compared to the title compound and which also exhibits different types of envelope conformations: In the title compound the isopropylidene unit is out of plane with the other four atoms constituting the five membered ring. In the methyl derivative it is the C-H group, and in the lactol, the methylene group, thus confirming that the energies of the different conformers of the dimethyldioxolane rings are indeed very close.
supplementary materials sup-2 For compound QEMKID (Zhao et al., 2006), which features a β connection at carbon C1, a different conformation is also found for the actual sugar with C1 and O1 changing their roles in the five membered ring (Figure 3c). Overall, the crystal structure of the title compound provides evidence that appending an ester group at C-1 does little to alter the conformation of the mannofuranose ring.

Refinement
Treatment of hydrogen atoms: Hydrogen atoms have been added in calculated positions with C-H bond lengths between 0.95 and 1.00 Å and have been refined with an isotropic displacement parameter of 1.5 times (CH 3 ) or 1.2 times (C-H and CH 2 ) that of the equivalent isotropic displacement parameter of the adjacent carbon atom. Methyl H atoms were allowed to rotate to best fit the experimental electron density.